Bone Regeneration Effect of Hyperbaric Oxygen Therapy Duration on Calvarial Defects in Irradiated Rats.

OBJECTIVE: In this study, we evaluated changes in bone remodeling in an irradiated rat calvarial defect model according to duration of hyperbaric oxygen therapy. MATERIALS AND METHODS: The 28 rats were divided into four groups. Radiation of 12 Gy was applied to the skull, and 5-mm critical size defects were formed on both sides of the skull. Bone grafts were applied to one side of formed defects. From the day after surgery, HBO was applied for 0, 1, and 3 weeks. At 6 weeks after bone graft, experimental sites were removed and analyzed for radiography, histology, and histomorphometry. RESULTS: Micro-CT analysis showed a significant increase in new bone volume in the HBO-3 group, with or without bone graft. When bone grafting was performed, BV, BS, and BS/TV all significantly increased. Histomorphometric analysis showed significant increases in %NBA and %BVN in the HBO-1 and HBO-3 groups, regardless of bone graft. CONCLUSION: Hyperbaric oxygen therapy was effective for bone regeneration with only 1 week of treatment.

Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain.

PURPOSE: There is mounting evidence that, in addition to angiogenesis, hypoxia-induced inflammation via the hypoxia-inducible factor 1α (HIF-1α)-CXC chemokine receptor 4 (CXCR4) pathway may contribute to the pathogenesis of late-onset, irradiation-induced necrosis. This study investigates the mitigative efficacy of an HIF-1α inhibitor, topotecan, and a CXCR4 antagonist, AMD3100, on the development of radiation necrosis (RN) in an intracranial mouse model. METHODS AND MATERIALS: Mice received a single-fraction, 50-Gy dose of hemispheric irradiation from the Leksell Gamma Knife Perfexion and were then treated with either topotecan, an HIF-1α inhibitor, from 1 to 12 weeks after irradiation, or AMD3100, a CXCR4 antagonist, from 4 to 12 weeks after irradiation. The onset and progression of RN were monitored longitudinally via noninvasive, in vivo magnetic resonance imaging (MRI) from 4 to 12 weeks after irradiation. Conventional hematoxylin-eosin staining and immunohistochemistry staining were performed to evaluate the treatment response. RESULTS: The progression of brain RN was significantly mitigated for mice treated with either topotecan or AMD3100 compared with control animals. MRI-derived lesion volumes were significantly smaller for both of the treated groups, and histologic findings correlated well with the MRI data. By hematoxylin-eosin staining, both treated groups demonstrated reduced irradiation-induced tissue damage compared with controls. Furthermore, immunohistochemistry results revealed that expression levels of vascular endothelial growth factor, CXC chemokine ligand 12, CD68, CD3, and tumor necrosis factor α in the lesion area were significantly lower in treated (topotecan or AMD3100) brains versus control brains, while ionized calcium-binding adapter molecule 1 (Iba1) and HIF-1α expression was similar, though somewhat reduced. CXCR4 expression was reduced only in topotecan-treated mice, while interleukin 6 expression was unaffected by either topotecan or AMD3100. CONCLUSIONS: By reducing inflammation, both topotecan and AMD3100 can, independently, mitigate the development of RN in the mouse brain. When combined with first-line, antiangiogenic treatment, anti-inflammation therapy may provide an adjuvant therapeutic strategy for clinical, postirradiation management of tumors, with additional benefits in the mitigation of RN development.

Histopathological and scintigraphic comparisons of the protective effects of L-carnitine and amifostine against radiation-induced late renal toxicity in rats.

1. The aim of the present study was to compare the protective effects of L-carnitine and amifostine against radiation-induced late nephrotoxicity using technetium-99m diethylenetriaminepentaacetic acid scintigraphy and histopathological examination. 2. Seventy-one Albino rats were randomly divided into six groups as follows: (i) AMI + RAD (n = 15), 200 mg/kg, i.p., amifostine 30 min prior to irradiation (a single dose of 9 Gy); (ii) LC + RAD (n = 15), 300 mg/kg, i.p., L-carnitine 30 min prior to irradiation; (iii) LC (n = 10), 300 mg/kg, i.p., L-carnitine 30 min prior to sham irradiation; (iv) AMI (n = 10), 200 mg/kg, i.p., amifostine 30 min prior to sham irradiation; RAD (n = 11), 1 mL/kg, i.p., normal saline 30 min prior to irradiation; and (vi) control (n = 10), 1 mL/kg, i.p., normal saline 30 min prior to sham irradiation. Scintigraphy was performed before treatment and again 6 months after treatment. Kidneys were examined by light microscopy and a histopathological scoring system was used to assess the degree of renal damage. 3. The main histopathological findings were proximal tubular damage and interstitial fibrosis. Glomerular injury was similar in all groups. Tubular degeneration and atrophy were less common in the AMI + RAD group than in the RAD group (P = 0.011 and P = 0.015, respectively), as well as in the LC + RAD group compared with the RAD group (P = 0.028 and P = 0.036, respectively). Interstitial fibrosis in the AMI + RAD and LC + RAD groups was significantly less than that in the RAD group (P = 0.015 and P = 0.015, respectively). The highest total renal injury score (9) was seen in the RAD group. On scintigraphy, there were significant differences in post-treatment time to peak count (T(max)) and time from peak count to half count (T((1/2))) values (P = 0.01 and 0.02, respectively) between groups in the right kidney. In the control and RAD groups, the T((1/2)) of the right kidney was 8 +/- 2 and 21 +/- 2 min, respectively. The T(max) values for the AMI + RAD and LC + RAD groups (2.8 +/- 0.2 and 3.2 +/- 0.2 min, respectively) were similar to those in the control group (2.5 +/- 0.3 min). 4. Based on the results of the present study, L-carnitine and amifostine have comparable and significant protective effects against radiation-induced late nephrotoxicity.

High-dose single-fraction brain irradiation: MRI, cerebral blood flow, electrophysiological, and histological studies.

Radiation-induced alterations in cerebrovascular and metabolic function form the basis for the radiosurgical treatment of selected intracranial vascular malformations and tumors in human patients. However, the underlying mechanisms, temporal progression, and modifying factors involved in the radiosurgical obliteration of these intracranial lesions as well as the risks of delayed radiation injury to surrounding normal brain remain poorly understood. In this report, the rabbit brain was used as an animal model to examine the effects of high-dose single-fraction X-irradiation on magnetic resonance imaging (MRI) appearance, neurophysiologic function, and histological integrity. At approximately 10 weeks following left-hemisphere irradiation with 60 Gy (225 kVp) X rays, MRI studies showed radiation-induced changes including blood-brain barrier (BBB) perturbations in the white matter regions and the hippocampus. Significant reductions in regional cerebral blood flow (rCBF) ratios were found in the hippocampus and certain regions of the cortex in irradiated animals. However, no changes in somatosensory evoked potentials (SEP) were observed. Histological studies demonstrated telangiectatic vessels, spreading edema in the white matter, and focal regions of necrosis and hemorrhage in the irradiated cortices and hippocampi. These results demonstrate that the irradiated rabbit brain may be used as an experimental model to correlate the spatiotemporal pattern of functional changes with radiologic and histological changes in delayed radiation injury.

[131 I accumulation in the thyroid gland of the rat following balneotherapy iodine dose administration]. / 131J-Speicherung in der Schilddrüse der Ratte nach kurmässig dosierter Jodzufuhr.

The effect of oral administration of iodine brine as used in the Austrian health resort Bad Hall on 131I uptake in thyroid, skin and serum, and on the renal radioiodine excretion was studied in 22 rats. Intake of iodine brine resulted in a marked decrease of 131I uptake by the thyroid, both in the long-term experiments (3 weeks of iodine brine supplementation, 131I administration 24 hours before the final evaluation) and in the short-term experiments (1 day iodine, 131I administration 2 hours before evaluation). Reductions in thyroid 131I uptake to 19.4% of the control uptake in the long-term and about 36% in the short-term experiments were observed. No alteration in 131I uptake was seen in the skin, whereas the radioiodine excretion in the urine was somewhat increased. The administration of iodide at a dosage easily achieved by drinking the iodine brine of Bad Hall is discussed as a protective measure against radiation hazards.